Tocilizumab in patients with active rheumatoid arthritis and inadequate responses to DMARDs and/or TNF inhibitors: a large, open-label study close to clinical practice

Abstract

Objective: To evaluate the safety and efficacy of tocilizumab in clinical practice in patients with rheumatoid arthritis (RA) with inadequate responses (IR) to disease-modifying antirheumatic drugs (DMARDs) or both DMARDs and tumour necrosis factor α inhibitors (TNFis).

Methods: Patients-categorised as TNFi-naive, TNFi-previous (washout) or TNFi-recent (no washout) -received open-label tocilizumab (8 mg/kg) every 4 weeks ± DMARDs for 24 weeks. Adverse events (AEs) and treatment discontinuations were monitored. Efficacy end points included American College of Rheumatology (ACR) responses, 28-joint disease activity score (DAS28) and European League Against Rheumatism responses.

Results: Overall, 1681 (976 TNF-naive, 298 TNFi-previous and 407 TNFi-recent) patients were treated; 5.1% discontinued treatment because of AEs. The AE rate was numerically higher in TNFi-recent (652.6/100 patient-years (PY)) and TNFi-previous (653.6/100PY) than in TNFi-naive (551.1/100PY) patients. Serious AE rates were 18.0/100PY, 28.0/100PY and 18.6/100PY; serious infection rates were 6.0/100PY, 6.8/100PY and 4.2/100PY, respectively. At week 4, 36.5% of patients achieved ACR20 response and 14.9% DAS28 remission (<2.6); at week 24, 66.9%, 46.6%, 26.4% and 56.8% achieved ACR20/ACR50/ACR70 responses and DAS28 remission, respectively. Overall, 61.6% (TNFi-naive), 48.5% (TNFi-previous) and 50.4% (TNFi-recent) patients achieved DAS28 remission.

Conclusions: In patients with RA who were DMARD-IR/TNFi-IR, tocilizumab ± DMARDs provided rapid and sustained efficacy without unexpected safety concerns.

Figure 1

Patients achieving ACR20/ACR50/ACR70 responses (A) (all patients had valid assessments to week 24. Missing data were imputed for joint counts only, and non-responder imputation was used (ie, when constituent data were missing, these were not included in response computations, and patients were classified as non-responders)), DAS28 LDA/<2.6 (B), or LDA/remission according to CDAI (C) or SDAI (D) criteria (missing data were imputed for joint counts only) over time (ITT population). ACR, American College of Rheumatology; CDAI, Clinical Disease Activity Index; DAS28, Disease Activity Score based on 28 joints; DMARD, disease-modifying anti-rheumatic drug; ITT, intention to treat; LDA, low disease activity; SDAI, simplified disease activity index; TNFi, tumour necrosis factor inhibitor; TNFi naive, patients who had never received TNFi therapy; TNFi previous use, patients who had discontinued TNFi therapy for >2 months before baseline (washout period); TNFi recent use, patients who had discontinued TNFi therapy for ≤2 months before baseline (no washout period).